MECHANISM OF OUTER HAIR CELL MOTILITY

这些研究的长期目标是阐明这种机制。 快速外毛细胞(OHC)的运动。结果将集中在 对基础研究有兴趣，因为他们会 描述了OHC的运动能力，以输入能量到 耳蜗骨。这是严肃的理论和实践的必要前提 OHC运动在耳蜗功能中作用的实验研究 和病理学。这些研究的一个重要的次要好处是它们 关于超高速运动对细胞生物学的贡献 一种不同于迄今为止在其他任何地方看到的机制。 提出了五项实验研究。其中三个是为了测试 从早期的研究中得出的机制的概念和 它们已经被表述成一个全面的数学模型。在……里面 这种模式，运动性被认为是由大量的 位于细胞膜上的独立作用的马达分子 细胞的侧壁。这些“马达”被认为可以改变构象。 以随机电压依赖的方式。一项研究将寻找 马达构型变化的证据在噪声统计中 单元格的平均长度。另一门是研究马达的动力学。 以以前在技术上不可能实现的速度激活。马达是 据信在轴向和径向起反相作用。这个 第三，拟议的研究将审查这一行动的一致性。一个 第四项研究将确定OHC的力量产生能力 负载过重。最后，在第五项研究中，OHC运动性将被用作 电压依赖性体细胞定位的测定方法 导电性。此外，模型研究还将得到扩展和更新 研究了可供选择的模型方案。模型研究将在#年进行。 与生理学研究并行，并将与之相辅相成。

The long-term objective of these studies is to elucidate the mechanism of fast outer hair cell (OHC) motility. The results will be of central interest in basic studies of cochlear mechanism, because they will delineate the capabilities of OHC motility for energy input to the cochlea. This is a necessary precondition for serious theoretical and experimental examination of the role of OHC motility in cochlear function and pathology. An important secondary benefit of these studies is their contribution to cell biology about an extraordinarily fast motility mechanism, one that is unlike anything seen elsewhere to date. Five experimental studies are proposed. Three are designed to test concepts of the mechanism that have been derived from earlier studies and that have been formulated into a comprehensive mathematical model. In this model, motility is thought to be driven by a large number of independently-acting motor molecules located in the membrane of the cell's lateral wall. These "motors" are thought to change conformation in a stochastic voltage-dependent manner. One study will look for evidence of motor conformation changes in the noise statistics of the cell's average length. Another will examine the kinetics of motor activation at speeds not previously technically possible. The motor is believed to act antiphasically in the axial and radial directions. The third proposed study will examine the consistency of this action. A fourth study will determine the force generating capability of the OHC under load. Finally, in a fifth study, OHC motility will be used as an assay to determine the somatic location of voltage-dependent conductances. In addition, the model studies will be extended and new alternative model schemes examined. The model studies will proceed in parallel with and will complement the physiological studies.